| First Author | Moiseenko A | Year | 2017 |
| Journal | Stem Cells | Volume | 35 |
| Issue | 6 | Pages | 1566-1578 |
| PubMed ID | 28370670 | Mgi Jnum | J:252380 |
| Mgi Id | MGI:6093630 | Doi | 10.1002/stem.2615 |
| Citation | Moiseenko A, et al. (2017) Origin and characterization of alpha smooth muscle actin-positive cells during murine lung development. Stem Cells 35(6):1566-1578 |
| abstractText | ACTA2 expression identifies pulmonary airway and vascular smooth muscle cells (SMCs) as well as alveolar myofibroblasts (MYF). Mesenchymal progenitors expressing fibroblast growth factor 10 (Fgf10), Wilms tumor 1 (Wt1), or glioma-associated oncogene 1 (Gli1) contribute to SMC formation from early stages of lung development. However, their respective contribution and specificity to the SMC and/or alveolar MYF lineages remain controversial. In addition, the contribution of mesenchymal cells undergoing active WNT signaling remains unknown. Using Fgf10(CreERT2) , Wt1(CreERT2) , Gli1(CreERT2) , and Axin2(CreERT2) inducible driver lines in combination with a tdTomato(flox) reporter line, the respective differentiation of each pool of labeled progenitor cells along the SMC and alveolar MYF lineages was quantified. The results revealed that while FGF10(+) and WT1(+) cells show a minor contribution to the SMC lineage, GLI1(+) and AXIN2(+) cells significantly contribute to both the SMC and alveolar MYF lineages, but with limited specificity. Lineage tracing using the Acta2-CreERT2 transgenic line showed that ACTA2(+) cells labeled at embryonic day (E)11.5 do not expand significantly to give rise to new SMCs at E18.5. However, ACTA2(+) cells labeled at E15.5 give rise to the majority (85%-97%) of the SMCs in the lung at E18.5 as well as alveolar MYF progenitors in the lung parenchyma. Fluorescence-activated cell sorting-based isolation of different subpopulations of ACTA2(+) lineage-traced cells followed by gene arrays, identified transcriptomic signatures for alveolar MYF progenitors versus airway and vascular SMCs at E18.5. Our results establish a new transcriptional landscape for further experiments addressing the function of signaling pathways in the formation of different subpopulations of ACTA2(+) cells. Stem Cells 2017;35:1566-1578. |
